Psychosomatics 44:83-84, February 2003
© 2003 The Academy of Psychosomatic Medicine
Olanzapine and Haloperidol: Potential for Neutropenia?
Nasreen Abdullah, M.D.,
Liouda Voronovitch, M.D.,
Stephen Taylor, B.M., and
Steven Lippmann, M.D., University of Louisville School of Medicine, Louisville, Ky.
TO THE EDITOR: Neutropenia and agranulocytosis are rare but serious and potentially life-threatening side effects associated with the use of many antipsychotic drugs.1 Olanzapine is usually well tolerated, with a low incidence of adverse events;2 however, some cases of olanzapine-induced hematological toxicity have been reported, giving an indication that the drug can cause neutropenia.1,3–5 The same rarely applies to haloperidol.5 Neutropenia in a benign physiological pattern also occurs.3 The following clinical vignette suggests the occurrence of neutropenia induced by olanzapine and/or haloperidol.
Case Report
Mr. A, a 21-year-old African American man, was hospitalized with agitation and auditory hallucinations. The results of admission toxicology screens, a urinalysis, blood chemistries, and a CBC were within normal ranges; his WBC count, however, was near the lower limit of normal, at 4.4x109 (normal range=4.5–10.8x109). Olanzapine, 20 mg/day orally, was prescribed. An adjunctive 10 mg/day of haloperidol and 2 mg/day of lorazepam were administered because of recurrent dangerous behaviors.
Mr. A was still agitated on day 5, so his olanzapine dose was increased to 30 mg/day. A repeat CBC revealed a WBC count of 2.6x109 with a 22% differential neutrophil count. Potential causes of leukopenia, such as infections, hematological disorders, and nutritional deficiencies, were ruled out. The development of neutropenia prompted the immediate discontinuation of olanzapine, haloperidol, and lorazepam. The next day, a hemogram revealed improvement: Mr. A's WBC count and granulocyte counts were 3.4x109 and 42%, respectively.
Risperidone, 4 mg/day orally, became Mr. A's sole pharmacotherapy. He was discharged on day 8, still taking risperidone, with a WBC count of 3.2x109 and a neutrophil count of 37%.
Discussion
The normal range of the WBC count in African American men is, on average, slightly lower than that of Caucasians;3 a range of 2.8–7.2x109 is described. Our patient had an initial WBC count that was low normal but acceptable for his ethnicity. His WBC and neutrophil counts dropped during treatment with the triple drug regimen and improved upon discontinuation. This suggests a causal relationship. Olanzapine has a potential etiology for neutropenia; case reports of olanzapine use being occasionally associated with leukopenia1,3–5 are well documented. Animal studies have indicated cytopenia at 10–17 times the maximum human olanzapine dose;5 however, correlation to human subjects has not been established. Decades of experience with haloperidol and reading the associated literature have revealed only very rare instances of hematoxicity.5 Lorazepam is not known to induce leukopenia.5
This clinical vignette does not prove an etiological relationship to the medicines, but no other etiologies for neutropenia were discovered. Either olanzapine or haloperidol could have caused a suppression of the WBC count, and olanzapine may be the more likely offender. The simultaneous influence of both agents is unknown. It may be advisable to monitor the CBC in olanzapine-treated individuals, especially when olanzapine is dispensed with haloperidol. A conclusive impression is made more difficult by the patient's racial predisposition to leukopenia. Further study is necessary to substantiate any relationship between neutropenia and either olanzapine or haloperidol or their combination.
REFERENCES
- Kodesh A, Finkel B, Lerner AG, Kretzmer G, Sigal M: Dose-dependent olanzapine-associated leukopenia: three case reports. Int Clin Psychopharmacol 2001; 16:117-119[Medline]
- Bettinger TL, Mendelson SC, Dorson PG, Crismon ML: Olanzapine-induced glucose dysregulation. Ann Pharmacother 2000; 34:865-867[Abstract]
- Gajawani P, Tesar GE: Olanzapine-induced neutropenia. Psychosomatics 2000; 41:150-151[Free Full Text]
- Naumann R, Felber W, Heilemann H, Reuster T: Olanzapine-induced agranulocytosis (letter). Lancet 1999; 354:566-567
- Physicians' Desk Reference, 56th ed. Oradell, NJ, Medical Economics, 2002, pp 1973-1978, 2334-2338
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